1. Field of the Invention
The present invention relates to a process for preparing enantiomerically pure xcex2-hydroxy esters by hydrogenation in the presence of ruthenium catalysts.
2. Description of the Related Art
The catalytic hydrogenation of ketones and xcex2-keto esters with Ru-diphosphine complexes is known (e.g. Burk et al., J. Am. Chem. Soc. 1995, 117, 4423; A. Mortreux et al., Tetrahedron: Asymmetry, 7(2), 379-82, 1996; Noyori et al., Angew. Chem., Int. Ed. Engl., 36(3), 285-288, 1997; WO 9713763 A1).
The catalytic transfer hydrogenation of ketones with formic acid/triethylamine complex as reducing agent and ruthenium catalysts is also known (P. Knochel et al., Tetrahedron Lett., 37(45), 8165-8168, 1996; Sammakia et al., J. Org. Chem., 62(18), 6104-6105, 1997 (isopropanol as reducing agent)).
A common feature of all these methods is that the ligands and catalysts used are very awkward to prepare. In the transfer hydrogenations, furthermore, it is not the inexpensive hydrogen which is used but isopropanol or formic acid/tertiary amines instead. When the latter is used in the reaction it makes workup more difficult and automatically produces acetone or carbon dioxide.
In addition, the amounts of catalyst employed in these reactions are generally very large; this makes the prior art processes uneconomic.
It is an object of the present invention to discover a process for hydrogenating keto esters which operates with hydrogen as reducing agent, uses a catalyst which is easy to prepare, permits a high substrate:catalyst ratio, and operates with high enantioselectivity.
We have found that this object is achieved by a process for preparing enantiomerically pure xcex2-hydroxy esters by reacting xcex2-keto esters with hydrogen in the presence of catalysts of the formula LRuX2 where
X is halogen, acetate, allyl, methallyl, 2-phenylallyl, per-chlorate, trifluoroacetate, tetrafluoroborate, hexafluoroan-timonate, hexafluorophosphate, hexafluoroarsenate, trichlo-roacetate,
L is a bidentate phospholane of the formula I 
xe2x80x83where
B=is a bridging link with 1-5 carbon atoms between the two phosphorus atoms,
R1=H, C1-C6-alkyl, aryl, alkylaryl or SiR23,
R2=alkyl or aryl,
m=0 or 1,
R3=H or OR4, and
R4=R1,
with the proviso that if m=1 then R3=H and if m=0 then R3xe2x89xa0H.
Preferred bridging links B are those where 
Particular preference is given to bridging links B where n=1 or 2 or r=0.
The preparation of the bidentate phospholane ligands L is described in patent applications DE 19725796.8 and DE 19824121.6 and in the experimental section of this specification.
The preparation starts from the sugar mannitol, which is available in enantiomerically pure form from natural sources.
The catalytically active ruthenium complexes LRuX2 can be prepared by conventional reaction (e.g. Uson, Inorg. Chim. Acta 73, 275 (1983), EP-A 0158875, EP-A 437690) with ruthenium complexes containing labile ligands (e.g. [RuCl2(COD)]n, p-cymene-ruthenium chloride dimer).
The hydrogenation of the invention is generally conducted at a temperature from xe2x88x9220 to 150xc2x0 C., preferably from 0 to 100xc2x0 C. and, with particular preference, from 15 to 40xc2x0 C.
For the hydrogenation process of the invention the hydrogen pressure can be varied within a wide range between 0.1 and 300 bar. Very good results are obtained within a pressure range from 1 to 100 bar, preferably from 1 to 50 bar.
The reaction is preferably conducted in a solvent which comprises an alkanol.
Preferred solvents for the hydrogenations are C1-C4-alkanols, especially MeOH. In the case of poorly soluble substrates suitability extends to solvent mixtures, such as methanol and CH2Cl2, THF, toluene, or else water.
It is particularly preferred to use the alkanol on which the xcex2-keto ester substrate is based, since this prevents unwanted transesterifications.
The catalyst is commonly employed in amounts of from 1:10 to 1:1,000,000, preferably from 1:1000 to 1:100,000 (w/w), based on the hydrogenation substrate.
The reaction can be improved in terms of both yield and selectivity by adding an acid, especially a strong acid, such as mineral acids or trifluoro- or trichloroacetic acids.
In this case the acid is generally added in an amount of 0.5-2 mol equivalents, based on catalyst.